ArticleScience signaling2013
Phenobarbital indirectly activates the constitutive active androstane receptor (CAR) by inhibition of epidermal growth factor receptor signaling.
Article in Science signaling, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 93 papers.
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Who cites it
93 citing papers in PubMed, 191 citations in OpenAlex.
- Analysis of transcriptomic alterations induced by 33 different per- and polyfluoroalkyl substances (PFAS) in differentiated HepaRG cells.Archives of toxicology · 2026Article
- Molecular characterization of the A52 murine hepatocellular carcinoma cell line.Animal models and experimental medicine · 2026Article
- CAR: Discovery and development by the pharmacogenetics laboratory at NIEHS, NIH.Pharmacological research · 2025Review
- Psychoactive substances: novel molecular insights and therapeutic potential for Alzheimer's disease.Translational neurodegeneration · 2025Review
- Chitosan Nanoparticles for Topical Drug Delivery in Chemotherapy-Induced Alopecia: A Comparative Study of Five Repurposed Pharmacological Agents.Pharmaceuticals (Basel, Switzerland) · 2025Article
- Machine Learning on Toxicogenomic Data Reveals a Strong Association Between the Induction of Drug-Metabolizing Enzymes and Centrilobular Hepatocyte Hypertrophy in Rats.International journal of molecular sciences · 2025Article
- Yinchenhao decoction alleviates obstructive jaundice liver injury by modulating epidermal growth factor receptor and constitutive androstane receptor signaling.World journal of hepatology · 2025Article
- Polybrominated diphenyl ether flame retardants inhibit growth factor-induced activation of EGFR by binding to its extracellular domain.Archives of toxicology · 2025Article
- HNF4α contributes to hepatic CAR dysfunction in polymicrobial sepsis.Frontiers in immunology · 2025Article
- Dioxins do not only bind to AHR but also team up with EGFR at the cell-surface: a novel mode of action of toxicological relevance?EXCLI journal · 2025Review
- Steatotic liver disease induced by TCPOBOP-activated hepatic constitutive androstane receptor: primary and secondary gene responses with links to disease progression.Toxicological sciences : an official journal of the Society of Toxicology · 2024Article
- Diindoles produced from commensal microbiota metabolites function as endogenous CAR/Nr1i3 ligands.Nature communications · 2024Article
- Phenobarbital in Nuclear Receptor Activation: An Update.Drug metabolism and disposition: the biological fate of chemicals · 2023Review
- Proteomic analysis of hepatic effects of phenobarbital in mice with humanized liver.Archives of toxicology · 2022Article
- Activation of Alternative Bilirubin Clearance Pathways Partially Reduces Hyperbilirubinemia in a Mouse Model Lacking Functional Ugt1a1 Activity.International journal of molecular sciences · 2022Article
- Protein phosphatase 2A regulates cytotoxicity and drug resistance by dephosphorylating AHR and MDR1.The Journal of biological chemistry · 2022Article
- Human CYP2B6 produces oxylipins from polyunsaturated fatty acids and reduces diet-induced obesity.PloS one · 2022Article
- Roles of cytochrome P450 enzymes in pharmacology and toxicology: Past, present, and future.Advances in pharmacology (San Diego, Calif.) · 2022Article
- Cytochrome P450 Enzymes and Drug Metabolism in Humans.International journal of molecular sciences · 2021Review
- Drug-Metabolizing Cytochrome P450 Enzymes Have Multifarious Influences on Treatment Outcomes.Clinical pharmacokinetics · 2021Review
33 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
Phenobarbital is a central nervous system depressant that also indirectly activates nuclear receptor constitutive active androstane receptor (CAR), which promotes drug and energy metabolism, as well as cell growth (and death), in the liver. We found that phenobarbital activated CAR by inhibiting epidermal growth factor receptor (EGFR) signaling. Phenobarbital bound to EGFR and potently inhibited the binding of EGF, which prevented the activation of EGFR. This abrogation of EGFR signaling induced the dephosphorylation of receptor for activated C kinase 1 (RACK1) at Tyr(52), which then promoted the dephosphorylation of CAR at Thr(38) by the catalytic core subunit of protein phosphatase 2A. The findings demonstrated that the phenobarbital-induced mechanism of CAR dephosphorylation and activation is mediated through its direct interaction with and inhibition of EGFR.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.